This project aims to develop a novel potential treatment for common neuropsychiatric disorders, specifically chronic pain syndrome and affective disorders including depression, anxiety, and post-traumatic stress disorder (PTSD). We have previously shown that real-time functional magnetic resonance imaging (rt-fMRI) can provide a feedback signal (neurofeedback) that allows people to gain learned voluntary control of activation in the rostral anterior cingulate (rACC), which in turn alters pain perception. Here, we aim to develop a brain-validated electroencephalography (EEG) neurofeedback method that involves simultaneous EEG and fMRI recordings. This system will then be used to determine EEG signatures reflective of regulation of rACC and of the amygdala. Multiple psychiatric states (e.g., depressive, anxious) are associated with an inability to regulate emotion and appear to be characterized by dysfunction of the limbic circuit including the ACC and amygdala. However, current psychiatric treatment approaches typically lack specificity regarding brain networks and mechanisms. Based on research studies indicating that individuals can be trained to regulate their own mental and physiological responses through online feedback, the proposed study aims to develop a novel tool for enhancing physiological resilience through psychological training using brain signals as the basis for such feedback. Thus, neurofeedback can provide a potential, complementary/alternate approach for treatment of neuropsychiatric disturbances. The combination of simultaneously acquired high spatial-resolution fMRI data and high temporal-resolution EEG data together with advanced statistical learning approaches provide a plausible way to infer and generate a robust and effective EEG neurofeedback signals that can target even deep brain structures such as the rACC or amygdala as the source of feedback. Given the high prevalence of psychopathology and the non-specific targeting of current treatments, the development of a robust method for learned regulation of specific limbic regions is important. Specifically, the new EEG-neurofeedback tool could be a novel, rational, neuroscience-based therapeutic intervention that could become a portable, easy-to-use, and low-cost clinical tool for improving self-control over brain working. In the long-term such a technique could be useful in alleviating chronic pain and regulating emotional instability and agony in cases of depression and anxiety syndromes. PUBLIC HEALTH RELEVANCE: The inability to self-regulate our affective/mental states is an underlying cause of multiple disorders, including chronic pain syndrome, depression, and anxiety that have serious social and psychological consequences. This project aims to develop a novel system that enables people to learn to regulate pain and emotion, which could lead to improved outcomes for major neuropsychiatric diseases that are often unresponsive to current treatments.